GRAPEFRUIT JUICE STEMS WEIGHT GAIN IN MICE FED A HIGH FAT DIET

Fad diets come and go, but might there be something to the ones that involve consuming grapefruit and grapefruit juice? New research at the University of California, Berkeley, suggests that a closer look at grapefruit juice is warranted.

A new study, to be published in the peer-reviewed journal PLOS ONE, found that mice fed a high-fat diet gained 18 percent less weight when they drank clarified, no-pulp grapefruit juice compared with a control group of mice that drank water. Juice-drinking mice also showed improved levels of glucose, insulin and a type of fat called triacylglycerol compared with their water-drinking counterparts.

If these findings sound somewhat familiar, it may be because the link between grapefruit juice and weight loss -- or just decreased weight gain -- has been touted in Hollywood diets before. However, the earlier studies behind those claims were often small, not well-controlled and contradictory, according to Andreas Stahl and Joseph Napoli, the two UC Berkeley faculty members who led the new research.

This latest work was funded by the California Grapefruit Growers Cooperative, but the UC Berkeley researchers emphasized that the funders had no control or influence over the study design or research findings. Both Stahl and Napoli said they went into this research with some skepticism.

"I was surprised by the findings," said Stahl, associate professor of nutritional sciences and toxicology. "We even re-checked the calibration of our glucose sensors, and we got the same results over and over again."

Napolli added that "we see all sorts of scams about nutrition. But these results, based on controlled experiments, warrant further study of the potential health-promoting properties of grapefruit juice."

Pitting juice against water

The study authors randomly divided mice into six groups, including a control group that drank only water. Those drinking grapefruit juice got a mixture diluted with water at different concentrations, and sweetened slightly with saccharin to counteract grapefruit's bitterness. The researchers also added glucose and artificial sweeteners to the control group's water so that it would match the calorie and saccharin content of the grapefruit juice.

At the end of the study period, the mice that ate the high-fat diet and drank diluted grapefruit juice not only gained less weight than their control counterparts, they also had a 13 to 17 percent decrease in blood glucose levels and a threefold decrease in insulin levels, which reveals greater sensitivity to insulin. (In Type 2 diabetes, the pancreas makes extra insulin to compensate for increased resistance to the hormone.)

The researchers gave one group of mice naringin, a bioactive compound in grapefruit juice that has been identified as a key agent in weight loss, and another group metformin, a glucose-lowering drug often prescribed for those with Type 2 diabetes.

The mice were fed a diet that was either 60 percent fat or 10 percent fat for 100 days, and their metabolic health was monitored throughout the study.

"The grapefruit juice lowered blood glucose to the same degree as metformin," said Napoli, professor and chair of nutritional sciences and toxicology. "That means a natural fruit drink lowered glucose levels as effectively as a prescription drug."

Weight effects only seen in high-fat diet

The group of high-fat-diet mice that received naringin had lower blood glucose levels than the control group, but there was no effect on weight, suggesting that some other ingredient in grapefruit juice is also beneficial.

"There are many active compounds in grapefruit juice, and we don't always understand how all those compounds work," said Stahl.

The study did not find as big an impact on mice that ate a low-fat diet. Those that drank the grapefruit juice saw a two-fold decrease in insulin levels, but there was no significant change in weight or other metabolic variables.

"The effects were more subtle for the low-fat diet group," explained Stahl. "Mice are incredibly healthy animals with naturally low levels of bad cholesterol. So if they are eating a healthy, low-fat diet, it will take more to see a significant effect on their health."

The researchers said they ruled out the typical explanations for weight loss in their study. It wasn't the amount of food consumed, since the ingested calories among the different groups were about the same. The level of activity and body temperatures were comparable, and the authors even checked the calories eliminated in the feces of the mice to check for problems with the body's absorption of nutrients.

"Basically, we couldn't see a smoking gun that could explain why or how grapefruit juice affects weight gain," said Stahl.

The researchers said they hope to continue the investigation into grapefruit juice. "Obesity and insulin resistance are such huge problems in our society, " said Stahl. "These data provide impetus to carry out more studies."

PROTEIN REGULATES BURNING OF BODY FAT

Muscle movements generate body heat. However, body heat can also be generated in another way: body fat contains a small number of brown adipose cells -- special fat cells that can generate heat without muscle activity. They do this using a protein known as UCP1 that enables babies or hibernating animals to keep warm without shivering. A research team at the University of Veterinary Medicine (Vetmeduni Vienna) has found that a specific chemical compound, an aldehyde, can activate UCP1 under certain conditions, and that could also trigger fat burning. The data were published in the journal PLoS One

The uncoupling Protein 1 (UCP1) is found exclusively in brown adipose tissue. Until some years ago it was thought that only babies and hibernating animals had brown adipose tissue, but since then it also has been found in adults, so UCP1 could be useful in the fight against obesity. "If we can find out how to regulate this protein, we might also find a way to trigger fat burning in the body," explains biophysicist Elena Pohl from the Unit of Physiology and Biophysics at the Vetmeduni Vienna.

UCP1 burns energy

UCP1 is located in the membrane of mitochondria, the power plants that fuel every single cell in the body. Cells that require a lot of energy, such as muscle cells, contain many mitochondria. But brown adipose tissue contains even more mitochondria than muscle tissue. In fact, it is the mitochondria that are responsible for the brown colour of this form of adipose tissue. Regular adipose tissue, which is the majority, is white. UCP1 in mitochondria uses the cell's energy to produce heat. If UCP1 is 'turned off' in mice, the animals will freeze. Hibernating animals would not survive the winter if they did not have this protein.

Researchers aim to regulate UCP1

Elena Pohl and her research group are trying to find a way to regulate UCP1. In a project funded by the FWF, they have tested different substances reported to activate UCP1, under them also reactive aldehyde 4-hydroxy-2-nonenal (HNE).Using an artificial cell membrane containing UCP1, the researchers were able to detect the activity of the protein by measuring the electrical conductivity on the membrane. The researchers dripped HNE onto the membrane and found that UCP1 can be activated by HNE only if combined with fatty acids. "In this model, all the 'players' are known so we could determine clearly whether the substance influences the protein directly or not. The discovery helps to improve our understanding of the mechanisms that regulate UCP1 and may even lead us to a way to burn body fat," explains co-author Olga Jovanovic.

Reducing free radicals

Free radicals play an important role in many biological processes, but they also cause cellular damage and play a crucial role in the pathogenesis of various diseases such as cancer, atherosclerosis and Alzheimer's disease. The research team has also shown that HNE, combined with fatty acids, also has the potential to minimize these damaging free radicals by reducing the membrane potential. "We want to elucidate the molecular mechanisms of UCP. We are still examining various aldehydes and other UCPs. There are five different UCPs and all their functions are not yet fully understood. We hope that our work will contribute to the development of therapies for various diseases."

Drugs in the battle against obesity

In the 1930s, a substance similar to UCP1 was developed that seemed to promise an easy way of losing weight. The substance was called 2,4-dinitrophenol and, like UCP1, it worked as an uncoupler in the mitochondria of cells. Taken in the right amounts, the drug accelerates the human metabolism by up to 50 percent. However, in some cases it caused serious or even lethal side effects and had to be withdrawn from the market. "If we are able to regulate UCP1 in a controlled way, it might be different story," says Pohl.

HIGH FAT DIET POSTPONES BRAIN AGING IN MICE

New Danish-led research suggests that signs of brain aging can be postponed in mice if placed on a high-fat diet. In the long term, this opens the possibility of treatment of children suffering from premature aging and patients with Alzheimer's and Parkinson's disease. The research project is headed by the Center for Healthy Aging, University of Copenhagen and the National Institute of Health.

When we get older, defects begin to develop in our nervous system, our brain loses some of its intellectual capacity, and the risk of developing diseases such as Parkinson's and Alzheimer's increases. Alzheimer's disease is currently the fastest-growing age-related disease.

Throughout our lives, it is important that our cells -- to the extent possible -- keep our DNA undamaged, and, therefore, the cells have a system that repairs the damage that occurs all the time. Humans age when the repair system ceases to function. In diseases such as Alzheimer's, the researchers also see damage to the DNA

A new research project headed by the Center for Healthy Aging, University of Copenhagen and the National Institute of Health has studied mice having a defect in their DNA repair system. In humans, this defect causes the disorder Cockayne syndrome, where patients prematurely age as children and die at an age of 10-12 years. The study shows that placing a mouse model of Cockayne syndrome on a high-fat diet will postpone aging processes such as impaired hearing and weight loss.

Fat putting a stop to premature aging

"The study is good news for children with Cockayne syndrome, because we do not currently have an effective treatment. Our study suggests that a high-fat diet can postpone aging processes. A diet high in fat also seems to postpone the aging of the brain. The findings therefore potentially imply that patients with Alzheimer's and Parkinson's disease in the long term may benefit from the new knowledge," says Professor Vilhelm Bohr from the Center for Healthy Aging, University of Copenhagen and the National Institute of Health, who has headed the study.

Our brain has a constant need for fuel in the form of either sugar or so-called ketones. Ketones are the brain's fuel reserve, and, in particular, play an important role in periods of low blood sugar levels, e.g. if you are fasting. This is because the body breaks down fat if it needs sugar, and during this process it produces ketones. The researchers see a particular positive effect when the mice are given the so-called medium chain fatty acids -- e.g. from coconut oil.

Brain cells need extra fuel

"In cells from children with Cockayne syndrome, we have previously demonstrated that aging is a result of the cell repair mechanism being constantly active. It eats into the resources and causes the cell to age very quickly. We therefore hope that a diet with a high content of coconut oil or similar fats will have a beneficial effect, because the brain cells are given extra fuel and thus the strength to repair the damage," says postdoc Morten Scheibye-Knudsen from the National Institute of Health.

The study has just been published in the scientific journal Cell Metabolism.